Chiral 1,3,2-oxazaborolidines have been well studied and regarded as important catalysts or reagents for the enantioselective reduction of prochiral ketones, imines and oximes, and in other stereoselective transformations. The development of oxazaborolidines has been driven mainly by the availability of suitable chiral aminoalcohols. Norephedrine and ephedrine are commercially available and relatively inexpensive in the two enantiomeric forms, and their derived oxazaborolidines have been reported as efficient chiral templates for the borane reduction of prochiral ketones and C═N double bonds, in catalytic hydroborations, as well as in additions of diethylzinc to aldehydes.
B—H oxazaborolidines are usually prepared by the reaction of norephedrine or ephedrine with borane-THF or borane dimethylsulfide complex. Their extreme sensitivity to air and moisture make these reagents difficult to purify by distillation or recrystallization and, consequently, they are commonly prepared in situ for subsequent reactions. However, side products present with the unpurified B—H heterocyclic catalysts or reagents cause a detrimental effect on the enantiomeric purity of desired chiral products. Furthermore, B—H oxazaborolidines can form dimers that alter the nature of the chiral catalyst. On the contrary, B-alkylated compounds are more stable, easier to purify and handle than the nonsubstituted counterparts, and produce similar enantioselectivities. B-substituted 1,3,2-oxazaborolidines are typically prepared by condensation of the aminoalcohols with boronic acids, boroxines, or their boronate esters, by removing water and boronic acid, or boronic ester residues, by azeotropic distillation in toluene. The treatment of chiral aminoalcohols with organo-bis(diisopropylamino)borane for the synthesis of B-alkyl and phenyl oxazaborolidines has also been reported. However, these methods require expensive and elaborated reagents, and moreover, the complete removal of water and boronic acid, or it derivatives, is extremely difficult.
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